12-56338841-A-C

Position:

• chr12-56338841-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000619177.1(IL23A):​n.108-585A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 385,098 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00046 (1 hom.)
• Consequence: IL23A ENST00000619177.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

Genes affected

IL23A (HGNC:15488): (interleukin 23 subunit alpha) This gene encodes a subunit of the heterodimeric cytokine interleukin 23 (IL23). IL23 is composed of this protein and the p40 subunit of interleukin 12 (IL12B). The receptor of IL23 is formed by the beta 1 subunit of IL12 (IL12RB1) and an IL23 specific subunit, IL23R. Both IL23 and IL12 can activate the transcription activator STAT4, and stimulate the production of interferon-gamma (IFNG). In contrast to IL12, which acts mainly on naive CD4(+) T cells, IL23 preferentially acts on memory CD4(+) T cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23A	NM_016584.3			upstream_gene_variant		ENST00000228534.6	NP_057668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23A	ENST00000619177.1	n.108-585A>C		intron_variant, non_coding_transcript_variant		2
IL23A	ENST00000622119.4	n.101-585A>C		intron_variant, non_coding_transcript_variant		2
IL23A	ENST00000228534.6			upstream_gene_variant		1	NM_016584.3	ENSP00000228534	P1

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 596 AN: 152048 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000455 AC: 106 AN: 232932 Hom.: 1 Cov.: 4 AF XY: 0.000399 AC XY: 47 AN XY: 117878

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.000858

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000197

Gnomad4 OTH exome AF: 0.000717

GnomAD4 genome AF: 0.00392 AC: 597 AN: 152166 Hom.: 2 Cov.: 31 AF XY: 0.00372 AC XY: 277 AN XY: 74396

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00532 Hom.: 0

Bravo AF: 0.00437

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs59094153; hg19: chr12-56732625;